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- PDB-10ri: Dimeric complex of VEGF, VEGFR2 and Neuropilin 1 -

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Basic information

Entry
Database: PDB / ID: 10ri
TitleDimeric complex of VEGF, VEGFR2 and Neuropilin 1
Components
  • Isoform VEGF-1 of Vascular endothelial growth factor A, long form
  • Neuropilin-1
  • Vascular endothelial growth factor receptor 2
KeywordsSIGNALING PROTEIN / VEGF / VEGFR / neuropilin
Function / homology
Function and homology information


positive regulation of lymphangiogenesis / VEGF-A complex / VEGF ligand-receptor interactions / VEGF binds to VEGFR leading to receptor dimerization / blood vessel endothelial cell differentiation / Neuropilin interactions with VEGF and VEGFR / bone trabecula formation / post-embryonic camera-type eye morphogenesis / cell migration involved in coronary vasculogenesis / trigeminal nerve morphogenesis ...positive regulation of lymphangiogenesis / VEGF-A complex / VEGF ligand-receptor interactions / VEGF binds to VEGFR leading to receptor dimerization / blood vessel endothelial cell differentiation / Neuropilin interactions with VEGF and VEGFR / bone trabecula formation / post-embryonic camera-type eye morphogenesis / cell migration involved in coronary vasculogenesis / trigeminal nerve morphogenesis / VEGFR2 mediated cell proliferation / Signal transduction by L1 / dichotomous subdivision of terminal units involved in salivary gland branching / regulation of bone development / regulation of hematopoietic progenitor cell differentiation / regulation of axon extension involved in axon guidance / regulation of endothelial cell differentiation / negative regulation of axon extension involved in axon guidance / basal dendrite development / otic placode development / CRMPs in Sema3A signaling / Sema3A PAK dependent Axon repulsion / basal dendrite arborization / regulation of endothelial cell proliferation / positive regulation of smooth muscle cell chemotaxis / retina vasculature morphogenesis in camera-type eye / vestibulocochlear nerve structural organization / dorsal root ganglion morphogenesis / lymphangiogenesis / ventral trunk neural crest cell migration / sympathetic neuron projection guidance / facioacoustic ganglion development / trigeminal ganglion development / sensory neuron axon guidance / basophil chemotaxis / lymph vessel morphogenesis / positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway / positive regulation of nitric oxide-cGMP mediated signal transduction / cellular stress response to acid chemical / : / facial nerve structural organization / trigeminal nerve structural organization / branchiomotor neuron axon guidance / vascular endothelial growth factor receptor 1 binding / negative regulation of adherens junction organization / gonadotrophin-releasing hormone neuronal migration to the hypothalamus / protein localization to early endosome / post-embryonic camera-type eye development / primitive erythrocyte differentiation / retina vasculature development in camera-type eye / positive regulation of mast cell chemotaxis / negative regulation of establishment of endothelial barrier / vascular endothelial growth factor receptor binding / negative regulation of blood-brain barrier permeability / lung vasculature development / VEGF-activated neuropilin signaling pathway / axon extension involved in axon guidance / positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway / motor neuron migration / eye photoreceptor cell development / renal artery morphogenesis / SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion / positive regulation of signal transduction / cellular response to hydrogen sulfide / endothelium development / endochondral bone growth / coronary vein morphogenesis / cardiac vascular smooth muscle cell development / lymph vessel development / neurofilament / regulation of vascular endothelial growth factor receptor signaling pathway / sympathetic neuron projection extension / mammary gland alveolus development / endocardium development / angiogenesis involved in coronary vascular morphogenesis / postsynapse organization / vascular endothelial growth factor binding / endothelial cell differentiation / vascular endothelial growth factor receptor-2 signaling pathway / endothelial tube morphogenesis / sympathetic ganglion development / negative regulation of axon extension / neural crest cell migration involved in autonomic nervous system development / axonogenesis involved in innervation / bone trabecula morphogenesis / vascular endothelial growth factor receptor activity / positive regulation of axon extension involved in axon guidance / endothelial cell chemotaxis / camera-type eye morphogenesis / positive regulation of protein localization to early endosome / Platelet degranulation / positive regulation of trophoblast cell migration / surfactant homeostasis / positive regulation of long-term neuronal synaptic plasticity / sympathetic nervous system development / retinal ganglion cell axon guidance / positive regulation of vasculogenesis / induction of positive chemotaxis / vascular wound healing / dopaminergic neuron differentiation
Similarity search - Function
Neuropilin / Neuropilin, C-terminal / C-terminal domain of neuropilin glycoprotein / Vascular endothelial growth factor receptor 2 (VEGFR2) / Vascular endothelial growth factor, heparin-binding domain / Vascular endothelial growth factor, heparin-binding domain superfamily / VEGF heparin-binding domain / VEGFR-2, transmembrane domain / : / VEGFR-2 Transmembrane domain ...Neuropilin / Neuropilin, C-terminal / C-terminal domain of neuropilin glycoprotein / Vascular endothelial growth factor receptor 2 (VEGFR2) / Vascular endothelial growth factor, heparin-binding domain / Vascular endothelial growth factor, heparin-binding domain superfamily / VEGF heparin-binding domain / VEGFR-2, transmembrane domain / : / VEGFR-2 Transmembrane domain / Vascular endothelial growth factor receptor 1-like, Ig-like domain / VEGFR-1-like, immunoglobulin-like domain / : / PDGF/VEGF domain / Platelet-derived growth factor, conserved site / PDGF/VEGF domain / Platelet-derived growth factor (PDGF) family signature. / Platelet-derived growth factor (PDGF) family profile. / Platelet-derived and vascular endothelial growth factors (PDGF, VEGF) family / MAM domain signature. / : / VEGFR1-3, N-terminal Ig-like domain / Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others) / : / MAM domain, meprin/A5/mu / MAM domain / MAM domain profile. / Coagulation factors 5/8 type C domain (FA58C) signature 2. / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Coagulation factors 5/8 type C domain (FA58C) signature 1. / CUB domain / Domain first found in C1r, C1s, uEGF, and bone morphogenetic protein. / CUB domain / Spermadhesin, CUB domain superfamily / CUB domain profile. / Coagulation factor 5/8 C-terminal domain, discoidin domain / Coagulation factors 5/8 type C domain (FA58C) profile. / F5/8 type C domain / Coagulation factor 5/8 C-terminal domain / Cystine-knot cytokine / Immunoglobulin domain / Immunoglobulin I-set / Immunoglobulin I-set domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Galactose-binding-like domain superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Immunoglobulin subtype / Immunoglobulin / Tyrosine-protein kinase, active site / Concanavalin A-like lectin/glucanase domain superfamily / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Vascular endothelial growth factor receptor 2 / Neuropilin-1 / Vascular endothelial growth factor A, long form
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsChen, L. / Bai, X. / Zhang, X.
Funding support United States, 4items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM130289 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM156386 United States
Robert A. Welch FoundationI-1702 United States
Robert A. Welch FoundationI-1944 United States
CitationJournal: Sci Adv / Year: 2026
Title: Mechanisms of VEGFR2 activation by VEGF, neuropilin, and heparin.
Authors: Lianqi Chen / Zhichen Sun / Jian Qiao / Xiao-Chen Bai / Xuewu Zhang /
Abstract: Vascular endothelial growth factor (VEGF) and its receptor VEGFR are master regulators of vasculogenesis and angiogenesis. VEGF activates VEGFR by inducing its dimerization and trans- ...Vascular endothelial growth factor (VEGF) and its receptor VEGFR are master regulators of vasculogenesis and angiogenesis. VEGF activates VEGFR by inducing its dimerization and trans-autophosphorylation. The coreceptor neuropilin (Nrp1 and Nrp2) and heparan sulfate proteoglycan (HSPG) modulate VEGF-VEGFR signaling, but the underlying mechanisms remain incompletely understood. Here we report a cryo-EM structure of the dimeric mouse VEGF-VEGFR2-Nrp1 ectodomain complex with a 2:2:2 stoichiometry, revealing direct Nrp1-VEGFR2 interactions that stabilize the VEGFR2 dimer. We also determined two cryo-EM structures of the VEGF-VEGFR2-Nrp1 complex in the presence of short- or long-chain heparin, which bridges all three proteins and promotes the formation of two distinct tetrameric complexes. Long-chain heparin induces a cis tetrameric complex consistent with receptor clustering on the same cell surface, whereas short-chain heparin promotes a trans tetrameric assembly which might be formed by two dimeric complexes from opposing cells. Our structure-based mutational analyses support the model that both the Nrp1-VEGFR2 interface and the heparin-mediated clustering enhance VEGFR2 signaling.
History
DepositionFeb 3, 2026Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 10, 2026Provider: repository / Type: Initial release
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Isoform VEGF-1 of Vascular endothelial growth factor A, long form
B: Isoform VEGF-1 of Vascular endothelial growth factor A, long form
C: Vascular endothelial growth factor receptor 2
E: Neuropilin-1
F: Neuropilin-1
D: Vascular endothelial growth factor receptor 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)402,68616
Polymers401,1996
Non-polymers1,48810
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Isoform VEGF-1 of Vascular endothelial growth factor A, long form / L-VEGF / Vascular permeability factor / VPF


Mass: 20787.742 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Vegfa, Vegf / Production host: Homo sapiens (human) / References: UniProt: Q00731
#2: Protein Vascular endothelial growth factor receptor 2 / VEGFR-2 / Fetal liver kinase 1 / FLK-1 / Kinase NYK / Protein-tyrosine kinase receptor flk-1


Mass: 84499.039 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Kdr, Flk-1, Flk1 / Production host: Homo sapiens (human)
References: UniProt: P35918, receptor protein-tyrosine kinase
#3: Protein Neuropilin-1 / A5 protein


Mass: 95312.578 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Nrp1, Nrp / Production host: Homo sapiens (human) / References: UniProt: P97333
#4: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#5: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Ca
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: dimeric complex of VEGF, VEGFR2 and Neuropilin 1 / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Molecular weightValue: 0.4 MDa / Experimental value: NO
Source (natural)Organism: Mus musculus (house mouse)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: NITROGEN

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1RELIONparticle selection
2PHENIX1.21rc1_4924model refinement
13RELION3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 64468 / Symmetry type: POINT
RefinementHighest resolution: 3.6 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00420792
ELECTRON MICROSCOPYf_angle_d0.69528200
ELECTRON MICROSCOPYf_dihedral_angle_d5.0322698
ELECTRON MICROSCOPYf_chiral_restr0.0513106
ELECTRON MICROSCOPYf_plane_restr0.0083644

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